Histological changes at 12 months in knee joints of Novdel3−/− males compared with Novdel3+/+ males. A, B: safranin O staining. Increased staining seen in the meniscus (m), articular cartilage (ac), collateral ligament (l), cruciate ligament (cl) and synovium (*) (A, B). Note expansion of fibrocartilage stained with safanin O in the collateral ligament (l) (A) and cruciate ligament (cl) (arrowheads) (B). C: H and E staining of joint margins showing the presence of osteophytic outgrowths (op) in Novdel3−/− males (C), but not in Novdel3+/+ control. D: Alkaline phosphatase staining of adjacent section shown in C. Positive staining of the osteophytes with the osteoblast marker alakaline phosphatase (AlkPhos) (D). E: Immunohistochemistry with anti-PCNA antibody, counterstained with haematoxlyin. Proliferating cells expressing PCNA (black arrowhead) were found in ligaments (l), synovium (s) and in the groups of cells in the margins of the meniscus in Novdel3−/− males. Negative cells indicated by white arrow. Scale bar 100 μm.